Ph-switchable hydrogel
Supramolecular polymers with controlled molecular weight and hydrogen-bonding units address the pH-switching limitations of existing hydrogels, enhancing their responsiveness for drug delivery and tissue interaction.
Patent Information
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- SUPRAPOLIX
- Filing Date
- 2026-04-23
- Publication Date
- 2026-07-17
AI Technical Summary
Existing supramolecular polymers used in hydrogels lack the ability to efficiently switch pH-responsive properties, limiting their applications in controlled drug delivery and tissue engineering.
Development of supramolecular polymers with specific molecular weight ranges and hydrogen-bonding units, allowing for precise control of polymer chain length and cross-linking, enhancing pH-responsive behavior.
The new supramolecular polymers exhibit enhanced pH-responsive properties, enabling effective control over drug release and tissue interaction, thus improving the efficacy of hydrogel-based therapies.
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Abstract
Description
Invention Title: pH Switching Hydrogel Abstract: This invention relates to supramolecular polymers comprising polymer chains according to formula (I): (I) wherein the average n in the supramolecular polymer is between 2 and 16, and wherein the constructing block *-Q-* represents: , wherein the average i in the supramolecular polymer is between 1.5 and 6.0, and wherein the constructing block *-T-* represents: , wherein the average j in the supramolecular polymer is between 1 and 6, wherein the average molecular weight Mn of the supramolecular polymer is between about 15 kDa and about 150 kDa, wherein POL is a linear hydrophilic polymer group with an average molecular weight Mn of about 1 kDa to about 30 kDa, wherein L and K represent linking groups, and wherein A represents a hydrogen-bonding unit. Abstract
Claims
CLAIMS1. Supramolecular polymer comprising polymer chains according to Formula (I):wherein:• the average n in the supramolecular polymer is between 2 and 16, one of the building blocks Q is connected to a terminal group via the bond marked with an asterisk, and one of the building blocks T is connected to a terminal group via the bond marked with an asterisk;• building block *-Q-* represents:wherein the average i in the supramolecular polymer is between 1.5 and 6.0;• building block *-T-* represents:wherein the average j in the supramolecular polymer is between 1 and 6;• the supramolecular polymer has an average molecular weight Mnof about 15 kDa to about 150 kDa, as determined with size-exclusion chromatography (SEC) with a GPC-system using RI detection with DMF comprising 10 mM LiBr at 50 °C as eluent, with the SEC-data being relative to PEO / PEG-standards;• POL is a linear hydrophilic polymeric group having an average molecular weight Mnof about 1 kDa to about 30 kDa;• moiety A represents moieties selected from the group consisting of Formulas (II- A) to (ILF), tautomers thereof and combinations thereof, wherein A is connected to L via the bonds marked with an asterisk in Formulas (ILA) to (ILF):(ILE) (ILF) each K is a urethane linking group; each L independently is a urethane or urea linking group, with the proviso that any moiety A according to Formula (ILA) and (ILB) is always coupled to a urea linking group L on the 2-position of the 4-pyrimidone, any moiety A according to Formula (ILC) and (ILD) is always coupled to a urea linking group L on the 2-position of the triazine, and any moiety A according to Formula (ILE) and (ILF) is always coupled to a urea linking group L on the 2-position of the pyrimidine; each R1is independently selected from the group consisting of hydrogen and Ci - C20 alkyl;• R2is selected from the group consisting of Ci - C20 alkylene, optionally substituted with O or S; and• R3is selected from the group consisting of linear or branched C2 - C20 alkylene groups and cyclic C3 - C24 alkylene groups.
2. Supramolecular polymer according to claim 1, wherein A in formula (I) represents the following moieties selected from the group consisting of Formula (II-A):wherein:R1is selected from the group consisting of hydrogen and Ci - C20 alkyl;Y is O or S; p is an integer of 1 to 20; and q is an integer of 0 to 8.
3. Supramolecular polymer according to claim 2, wherein R1is methyl and: a) p is 2 and q is 0; b) p is 2, q is 1 and Y is O; or c) p is 4 to 11 and q is 0.
4. Supramolecular polymer according to any one of claims 1 to 3, wherein:• any moiety A according to Formula (II-A) and (II-B) is coupled to a urea linking group L on the 2-position of the 4-pyrimidone and to a urethane urea linking group L on the 5-position of the 4-pyrimidone;• any moiety A according to Formula (II-C) and (II-D) is coupled to a urea linking group L on the 2-position of the triazine and to a urethane linking group L on the 4-position of the triazine,any moiety A according to Formula (II-E) and (II-F) is coupled to a urea linking group L on the 2-position of the pyrimidine and to a urethane linking group L on the 4-position of the pyrimidine.
5. Supramolecular polymer according to any one of claims 1 to 4, wherein R3is selected from selected from hexylene,6. Supramolecular polymer according to any one of claims 1 to 5, wherein POL is a linear polyethylene glycol having an average molecular weight Mnof between 10 kDa and 25 kDa.
7. Process for the manufacture of a supramolecular polymer by reacting, optionally in a non-reactive solvent, a compound A’ selected from the group consisting of Formulas (HI- A) to (III-F), tautomers thereof and combinations thereof with a diisocyanate compoundC’ according to the Formula O=C=N-R3-N=C=O and a polymer HO-POL-OH:(III-E) (III-F), wherein R1, R2, R3and POL are as defined in any one of claims 1 to 6, wherein FG1represents a functional group selected from OH and NH2, preferably OH, wherein the molar ratio of compound A’ to HO-POL-OH applied during the reaction is between 1.5 : 1.0 and 6.0 : 1.0, and wherein the molar ratio of compound C’ to the sum of compound A’ and HO-POL-OH applied during the reaction is between 1.1 : 1.0 and 0.9 : 1.0.
8. Process according to claim 7, wherein A’ represents moi eties selected from the group consisting of Formula (III-A):wherein:R1is selected from the group consisting of hydrogen and Ci - C20 alkyl;Y is O or S; p is an integer of 1 to 20; and q is an integer of 0 to 8.
9. Process according to claim 8, wherein R1is methyl and: a) p is 2, q is 0 and FG1is OH; b) p is 2, q is 1, Y is O and FG1is OH; c) p is 4 to 11, q is 0 and FG1is OH; or d) p is 4 to 11, q is 0 and FG1is NH2.
10. Process according to any one of claims 7 to 9, wherein molar ratio of compound A’ to HO-POL-OH is between 1.5 : 1.0 and 4.0 : 1.0.
11. Process according to any one of claims 7 to 10, wherein the supram olecular polymer produced is a supramolecular polymer according to Formula (I) as defined in any one of claims 1-6.
12. Supramolecular polymer obtainable by the process according to any one of claims 7 to 11.
13. Hydrogel formulation comprising 50.0 - 99.7 wt.% of water, 0.3 - 50.0 wt.% of the supramolecular polymer according to any one of claims 1 to 6 or 12, and 0 - 30 wt.% of further ingredients, based on the weight of the hydrogel formulation, wherein the amounts of water, supramolecular polymer and further ingredients add up to 100 wt.% of the hydrogel formulation.
14. Hydrogel formulation according to claim 13, which comprises 0.9 - 10.0 wt.% of the supramolecular polymer according to any one of claims 1 to 6 or 12, based on the weight of the hydrogel formulation.
15. Hydrogel formulation according to claim 13 or 14, which has a pH between 8.5 and 14.0 and is a liquid at a temperature between 20 and 40 °C.
16. Hydrogel formulation according to claim 15, having a pH between 8.5 and 14.0 and having a dynamic viscosity at 37 °C of between 0.01 and 20 Pa-s, as measured with a rheometer with a plate-plate geometry at a shear rate of 1 s'1and with a gap distance of 0.50 mm.
17. Hydrogel formulation according to claims 13 or 14, having, at a pH between 2.0 and less than 8.0:(i) storage moduli G’ of at least 20 Pa, preferably at least 200 Pa, most preferably at least 2000 Pa, across a frequency range of 0.2 to 20 Hz; and / or(ii) tan(b) values of lower than 0.2, preferably between 0.05 and 0.15, across a frequency range of 0.2 to 20 Hz, wherein the storage moduli G’ and tan(b) values are measured with a rheometer with a plate-plate geometry and a gap distance of 0.50 mm, at oscillatory frequencies between 0.2 and 20 Hz and at a temperature of 37 °C.
18. Hydrogel formulation according to any of claims 13 - 17, which comprises 0.0001 to 30 wt.% of one or more pharmaceutically active ingredients, based on the weight of the hydrogel formulation.
19. Hydrogel formulation according to claim 15 or 16, comprising 0.0001 to 30 wt.% of one or more pharmaceutically active ingredients, based on the weight of the hydrogel formulation, for use in the treatment of oncological diseases, cardio-vascular diseases, orthopaedic diseases, gastrointestinal diseases or wound care in mammalian subjects, said treatment comprising injecting the hydrogel formulation into the mammalian body, followed by release of the one or more pharmaceutically active ingredients from the hydrogel formulation.
20. Hydrogel formulation according to claim 15 or 16, comprising 0.0001 to 30 wt.% of one or more pharmaceutically active ingredients, based on the weight of the hydrogel formulation, for use in a method of prevention of tissue adhesion or in reconstructive surgery or cosmetic surgery in mammalian subjects, said method comprising injecting the hydrogel formulation into the mammalian body, followed by release of the one or more pharmaceutically active ingredients from the hydrogel formulation.
1. Hydrogel formulation according to claim 19 or 20, wherein the one or more pharmaceutically active ingredients are selected from the group consisting of anti-tumor agents, chemotherapeutic agents, local anesthetics and combinations thereof.